X-ray structure of peptidyl-prolyl cis-trans isomerase A from Mycobacterium tuberculosis.
Peptidyl-prolyl cis-trans isomerases (EC 18.104.22.168) catalyse the interconversion of cis and trans peptide bonds and are therefore considered to be important for protein folding. They are also thought to participate in processes such as signalling, cell surface recognition, chaperoning and heat-shock response. Here we report the soluble expression of recombinant Mycobacterium tuberculosis peptidyl-prolyl cis-trans isomerase PpiA in Escherichia coli, together with an investigation of its structure and biochemical properties. The protein was shown to be active in a spectrophotometric assay, with an estimated kcat/Km of 2.0 x 10(6) m(-1).s(-1). The X-ray structure of PpiA was solved by molecular replacement, and refined to a resolution of 2.6 A with R and Rfree values of 21.3% and 22.9%, respectively. Comparisons to known structures show that the PpiA represents a slight variation on the peptidyl-prolyl cis-trans isomerase fold, previously not represented in the Protein Data Bank. Inspection of the active site suggests that specificity for substrates and cyclosporin A will be similar to that found for most other enzymes of this structural family. Comparison to the sequence of the second M. tuberculosis enzyme, PpiB, suggests that binding of peptide substrates as well as cyclosporin A may differ in that case.


Direct Detection and Discrimination of Nucleotide Polymorphisms Using Anthraquinone Labeled DNA Probes.
A novel electrochemical detection approach using DNA probes labeled with Anthraquinone (AQ) as a reporter moiety has been successfully exploited as a method for the direct detection of DNA targets. This assay uses simple voltammetry techniques (Differential Pulse Voltammetry) to exploit the unique responsiveness of AQ to its chemical environments within oxygenated aqueous buffers, providing a specific detection mechanism as a result of DNA hybridization. This measurement is based on a cathodic shift of the reduction potential of the AQ tag and the concurrent reduction in peak current upon DNA binding. The further utility of this approach for discrimination of closely related DNA targets is demonstrated using DNA strands specific to B. anthracis and closely related bacillus species. DNA targets were designed to the rpoB gene incorporating nucleotide polymorphisms associated with different bacillus species. This assay was used to demonstrate that the shift in reduction potential is directly related to the homology of the target DNA. The discriminatory mechanism is dependent on the presence of oxygen in the measurement buffer and is strongly linked to the position of the nucleotide polymorphisms; with homology at the terminus carrying the AQ functionalised nucleotide critical to achieving accurate discrimination. This understanding of assay design was used to demonstrate an optimized assay capable of discriminating between Yersinia pestis (the causative agent of plague) and closely related species based on the groEL gene. This method is attractive as it can not only detect DNA binding, but can also discriminate between multiple Single Nucleotide Polymorphisms (SNPs) within that DNA without the need for any additional reagents, reporters, or processes such as melting of DNA strands. This indicates that this approach may have great potential to be exploited within novel biosensors for detection and diagnosis of infectious disease in future Point of Care (PoC) devices.


ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic?
Defects of coenzyme Q10 (CoQ10) metabolism cause a variety of disorders ranging from isolated myopathy to multisystem involvement. ADCK3 is one of several genes associated with CoQ10 deficiency that presents with progressive cerebellar ataxia, epilepsy, migraine and psychiatric disorders. Diagnosis is challenging due to the wide clinical spectrum and overlap with other mitochondrial disorders. A detailed description of three new patients and one previously reported patient from three Norwegian families with novel and known ADCK3 mutations is provided focusing on the epileptic semiology and response to treatment. Mutations were identified by whole exome sequencing and in two measurement of skeletal muscle CoQ10 was performed. All four patients presented with childhood-onset epilepsy and progressive cerebellar ataxia. Three patients had epilepsia partialis continua and stroke-like episodes affecting the posterior brain. Electroencephalography showed focal epileptic activity in the occipital and temporal lobes. Genetic investigation revealed ADCK3 mutations in all patients including a novel change in exon 15: c.T1732G, p.F578V. There was no apparent genotype-phenotype correlation. ADCK3 mutations can cause a combination of progressive ataxia and acute epileptic encephalopathy with stroke-like episodes. The clinical, radiological and electrophysiological features of this disorder mimic the phenotype of polymerase gamma (POLG) related encephalopathy and it is therefore suggested that ADCK3 mutations be considered in the differential diagnosis of mitochondrial encephalopathy with POLG-like features.


Dietary fructooligosaccharides and potential benefits on health.
Fructooligosaccharides (FOS) are oligosaccharides that occur naturally in plants such as onion, chicory, garlic, asparagus, banana, artichoke, among many others. They are composed of linear chains of fructose units, linked by beta (2-1) bonds. The number of fructose units ranges from 2 to 60 and often terminate in a glucose unit. Dietary FOS are not hydrolyzed by small intestinal glycosidases and reach the cecum structurally unchanged. There, they are metabolized by the intestinal microflora to form short-chain carboxylic acids, L -lactate, CO(2), hydrogen and other metabolites. FOS have a number of interesting properties, including a low sweetness intensity; they are also calorie free, non-cariogenic and are considered as soluble dietary fibre. Furthermore, FOS have important beneficial physiological effects such as low carcinogenicity, a prebiotic effect, improved mineral absorption and decreased levels of serum cholesterol, triacylglycerols and phospholipids. Currently FOS are increasingly included in food products and infant formulas due to their prebiotic effect stimulate the growth of nonpathogenic intestinal microflora. Their consumption increases fecal bolus and the frequency of depositions, while a dose of 4-15 g/day given to healthy subjects will reduce constipation, considered one of the growing problems of modern society, and newborns during the first months of life.


High-speed three-dimensional shape measurements of objects with laser speckles and acousto-optical deflection.
Many three-dimensional (3D) shape measurement techniques in stereophotogrammetry with temporal coded structured illumination are limited to static scenes because the time for measurement is too long in comparison to the object speed. The measurement of moving objects result in erroneous reconstructions. This is apparent to reduce measurement time to overcome this limitation, which is often done by increasing the projection rate for illumination while shrinking the amount of images taken for reconstruction. The projection rate limits most applications in its speed because digital light processing (DLP) projectors, which are widely used, bring a limited projection rate along. Our approach, in contrast, does not take a DLP. Instead we use laser speckles as projected patterns which are switched using an acousto-optical deflector. The projection rate is 10× higher than what the fastest stripe projection systems to our knowledge achieve. Hence, we present this uncommon but potential approach for highspeed (≈250 3Dfps= [3D measurements per second]), dense, and accurate 3D measurements of spatially separated objects and show the media that emphasizes the ability of accurate measurements while the objects under testing move.


[Use of "non-standard" young rabbits of the chinchilla breed for determination of the stereotaxic coordinates of brain structures].
It has been found that differences in the distances from the brain structures to orienting points on the scull of non-standard rabbits considerably exceed those in the distances between the brain structures of the same animals. In non-standard rabbits of one and the same age, the quantitative differences of the rostral or caudal location of all brain structures in relation to the bone orienting points are more significant than those in the lengths of the brain. Intravital determination of a point on the surface of the scull with horizontal coordinates of the anterior commissure is suggested for selection of young rabbits with a normal location of brain structures in regard to the zero point (bregma ) as well as for introduction of corrections in the location of the zero points. It is also suggested that this point be used directly as the zero point of reading the coordinates instead of the bregma.


Impact of poor retention in HIV medical care on time to viral load suppression.
The purpose of this study was to evaluate how poor retention in HIV care impacts time to viral suppression after initiating highly active antiretroviral therapy. A retrospective cohort study design, employing a medical chart review, was conducted at an academic infectious disease clinic at the University of Kentucky. Patients seeking care between 2003 and 2011 were included in the study. A log-normal model was employed to determine the factors associated with time to viral suppression. Of the 532 patients in the study, 426 (80.1%) patients were virally suppressed. Controlling for insurance status, race, baseline CD4 counts, and viral loads, the expected time to viral suppression for non optimal retainers was longer compared to optimal retainers (100% retained in care; time ratio: 2.04; 95% confidence interval: 1.40-2.90). Researchers should continue to study the impact of retention on clinical outcomes and strategies to improve retention and reengage those lost to follow-up back into care.


Colorectal sensation and motility.
To critically evaluate recent advances in the anatomy and physiology of colorectal motility and sensation and to discuss their potential clinical implications. Relatively noninvasive methods for the assessment of colonic transit have been developed and validated and high-resolution colonic and anorectal manometry as well as the barostat, despite their technical challenges, are beginning to show promise in clinical practice. At a more basic level, the importance of interstitial cells of Cajal as pacemakers, neuromodulators and stretch receptors has been revealed and their dysfunction associated with a number of disease states. Although the impact of a variety of biologically active agents on colonic sensorineural function in vitro has been described, the clinical implications of most of these effects remain unknown at this time. As the molecular bases of colonic motor and sensory function are identified, new disease entities are being described and novel therapeutic targets revealed. Equally important is the growing recognition of luminal factors and of the colonic microbiota, in particular, in the generation and modulation of colonic motility and sensation. The complexities of the basic physiology of colorectal motility and sensation continue to be revealed and our understanding of their regulation has progressed; clinical implications remain at a preliminary stage. Progress has been made, however, in the clinical assessment of colonic motor function.


Symbols Are Special: An fMRI Adaptation Study of Symbolic, Nonsymbolic, and Non-Numerical Magnitude Processing in the Human Brain.
How are different formats of magnitudes represented in the human brain? We used functional magnetic resonance imaging adaptation to isolate representations of symbols, quantities, and physical size in 45 adults. Results indicate that the neural correlates supporting the passive processing of number symbols are largely dissociable from those supporting quantities and physical size, anatomically and representationally. Anatomically, passive processing of quantities and size correlate with activation in the right intraparietal sulcus, whereas symbolic number processing, compared with quantity processing, correlates with activation in the left inferior parietal lobule. Representationally, neural patterns of activation supporting symbols are dissimilar from neural activation patterns supporting quantity and size in the bilateral parietal lobes. These findings challenge the longstanding notion that the culturally acquired ability to conceptualize symbolic numbers is represented using entirely the same brain systems that support the evolutionarily ancient system used to process quantities. Moreover, these data reveal that regions that support numerical magnitude processing are also important for the processing of non-numerical magnitudes. This discovery compels future investigations of the neural consequences of acquiring knowledge of symbolic numbers.


Molecular cloning of MSRG-11 gene related to apoptosis of mouse spermatogenic cells.
Beginning with a new contig of the expressed sequence tags (Mm.63892) obtained by comparing testis libraries with other tissue and cell line libraries using the digital differential display program, we cloned a new gene which is related to the apoptosis of mouse spermatogenic cells using the Genscan program and polymerase chain reaction (PCR) technology. The sequence data have been submitted to the GenBank database under accession number AY747687. The full cDNA length is 1074 bp, and the gene with 7 exons and 6 introns is located in mouse chromosome 1 H5. The protein is recognized as a new member of calmodulin (CaM) binding protein family because the sequence contains three short calmodulin-binding motifs containing conserved Ile and Gln residues (IQ motif) and is considered to play a critical role in interactions of IQ motif-containing proteins with CaM proteins. The putative protein encoded by this gene has 192 amino acid residues with a theoretical molecular mass of 23.7 kDa and a calculated isoelectric point of 9.71. The sequence shares no significant homology with any known protein in databases. RT-PCR and Northern blot analyses revealed that 1.3 kb MSRG-11 transcript was strongly expressed in adult mouse testis but weakly expressed in the spleen and thymus. The MSRG-11 gene was expressed at various levels, faintly at two weeks postpartum and strongly from three weeks postpartum in adult testes. The green fluorescence produced by pEGFP-C2/MSRG-11 was detected in the cytoplasm of COS7 cells 24 h post-transfection. The pcDNA3.1(?-)/MSRG-11 plasmid was constructed and introduced into COS7 cells using Lipofectamine 2000 transfection reagent (Invitrogen, Carlsbad, USA). MSRG-11 can accelerate COS7 cell apoptosis, which suggests that this gene may play an important role in the development of mouse testes and is a candidate gene of testis-specific apoptosis. Based on these observations, it was considered that we cloned a new gene which probably accelerates spermatogenetic cell apoptosis in mouse.


Bone and joint disease around the world. The Japan Rheumatism Friendship Association.
The Japan Rheumatism Friendship Association (JRFA) was founded in 1960 and today has a membership of about 23,000, with 47 chapters across the country. We periodically conduct a survey of our membership for the Rheumatism White Paper, which we have been publishing since the JRFA was formed. The entire membership is surveyed every 5 years; surveys give an accurate picture of the current state of the disease and reflect the fundamental activities of the JRFA; they shed light on progress in developing effective measures against arthritis, and give people a better understanding of rheumatism. The survey is also a unique resource, for it canvasses a wide cross section of people with arthritis. In Japan, the Rheumatism White Paper is widely regarded as an authoritative source. The aims of the JRFA are to promote the accurate knowledge of RA to improve mutual friendship, and to work for the establishment and development of policies against RA disease. In this way, the JRFA seeks to advance the welfare of RA patients. In this article the activities of the JRFA are described.


Influence of moonlight on mRNA expression patterns of melatonin receptor subtypes in the pineal organ of a tropical fish.
The goldlined spinefoot, Siganus guttatus, is a lunar-synchronized spawner, which repeatedly releases gametes around the first quarter moon during the reproductive season. A previous study reported that manipulating moonlight brightness at night disrupted synchronized spawning, suggesting involvement of this natural light source in lunar synchronization. The present study examined whether the mRNA expression pattern of melatonin receptor subtypes MT1 and Mel1c in the pineal organ of the goldlined spinefoot is related to moonlight. Real-time quantitative polymerase chain reaction analysis revealed that the abundance of MT1 and Mel1c mRNA at midnight increased during the new moon phase and decreased during the full moon phase. Exposing fish to moonlight intensity during the full moon period resulted in a decrease in Mel1c mRNA abundance within 1h. Fluctuations in the melatonin receptor genes according to changes in the moon phase agreed with those of melatonin levels in the blood. These results indicate that periodic changes in cues from the moon influence melatonin receptor mRNA expression levels. The melatonin-melatonin receptor system may play a role in predicting the moon phase through changes in night brightness.


Cross-cultural adaptation and validation to Brazil of the Obesity-related Problems Scale.
To validate a reliable version of the Obesity-related Problems Scale in Portuguese to use it in Brazil. The Obesity-related Problems Scale was translated and transculturally adapted. Later it was simultaneously self-applied with a 12-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), to 50 obese patients and 50 non-obese individuals, and applied again to half of them after 14 days. The Obesity-related Problems scale was able to differentiate obese from non-obese individuals with higher accuracy than WHODAS 2.0, correlating with this scale and with body mass index. The factor analysis determined a two-dimensional structure, which was confirmed with χ2/df=1.81, SRMR=0.05, and CFI=0.97. The general a coefficient was 0.90 and the inter-item intra-class correlation, in the reapplication, ranged from 0.75 to 0.87. The scale proved to be valid and reliable for use in the Brazilian population, without the need to exclude items.


phyA-GFP is spectroscopically and photochemically similar to phyA and comprises both its native types, phyA' and phyA''.
Low-temperature fluorescence investigations of phyA-GFP used in experiments on its nuclear-cytoplasmic partitioning were carried out. In etiolated hypocotyls of phyA-deficient Arabidopsis thaliana expressing phyA-GFP, it was found that it is similar to phyA in spectroscopic parameters with both its native types, phyA' and phyA'', present and their ratio shifted towards phyA'. In transgenic tobacco hypocotyls, native phyA and rice phyA-GFP were also identical to phyA in the wild type whereas phyA-GFP belonged primarily to the phyA' type. Finally, truncated oat Δ6-12 phyA-GFP expressed in phyA-deficient Arabidopsis was represented by the phyA' type in contrast to full-length oat phyA-GFP with an approximately equal proportion of the two phyA types. This correlates with a previous observation that Δ6-12 phyA-GFP can form only numerous tiny subnuclear speckles while its wild-type counterpart can also localize into bigger and fewer subnuclear protein complexes. Thus, phyA-GFP is spectroscopically and photochemically similar or identical to the native phyA, suggesting that the GFP tag does not affect the chromophore. phyA-GFP comprises phyA'-GFP and phyA''-GFP, suggesting that both of them are potential participants in nuclear-cytoplasmic partitioning, which may contribute to its complexity.


Bifocal optical coherenc refractometry of turbid media.
We propose and demonstrate a novel technique, which we term bifocal optical coherence refractometry, for the rapid determination of the refractive index of a turbid medium. The technique is based on the simultaneous creation of two closely spaced confocal gates in a sample. The optical path-length difference between the gates is measured by means of low-coherence interferometry and used to determine the refractive index. We present experimental results for the refractive indices of milk solutions and of human skin in vivo. As the axial scan rate determines the acquisition time, which is potentially of the order of tens of milliseconds, the technique has potential for in vivo refractive-index measurements of turbid biological media under dynamic conditions.


The suppressive influence of SMA on M1 in motor imagery revealed by fMRI and dynamic causal modeling.
Although motor imagery is widely used for motor learning in rehabilitation and sports training, the underlying mechanisms are still poorly understood. Based on fMRI data sets acquired with very high temporal resolution (300 ms) under motor execution and imagery conditions, we utilized Dynamic Causal Modeling (DCM) to determine effective connectivity measures between supplementary motor area (SMA) and primary motor cortex (M1). A set of 28 models was tested in a Bayesian framework and the by-far best-performing model revealed a strong suppressive influence of the motor imagery condition on the forward connection between SMA and M1. Our results clearly indicate that the lack of activation in M1 during motor imagery is caused by suppression from the SMA. These results highlight the importance of the SMA not only for the preparation and execution of intended movements, but also for suppressing movements that are represented in the motor system but not to be performed.


Steam versus hot-water scalding in reducing bacterial loads on the skin of commercially processed poultry.
A comparison of two types of scalders was conducted to determine their effectiveness in reducing bacterial contamination of poultry carcasses. A conventional hot-water scalder and a prototype model of a steam scalder were tested under commercial conditions. Total plate counts from steam-scalded birds were significantly lower than the counts of water-scalded birds immediately after scalding and again after picking. No differences in the two methods could be found after chilling. Coliform counts from steam-scalded birds were significantly lower than the counts from water-scalded birds immediately after scalding. No significant differences in coliform counts were detected when the two scald methods were compared after defeathering and chilling.


Tumefactive Demyelination Lesions: Report on three cases.
Tumefactive demyelination (TD) lesion and its subtype Balo's concentric sclerosis (BCS), are rare manifestations of central nervous system demyelinating disease. Because of its rarity, physicians might hesitate in reaching a diagnosis or initiating steroid pulse therapy. This study aims at pinpointing the key neuroimaging features to distinguish TD lesions from surgical conditions, and illustrating the clinical outcomes of patients with TD lesions. Two of the three patients had solitary TD lesions, one 47-year-old man presenting with newly onset seizure and another 54-year-old women suffering from progressive hemiparesis. The male patient underwent craniotomy for mass excision without further steroid therapy, while the female patient received methylprednisolone pulse therapy only. Both patients remained free of clinical and radiological relapses over the past 6-7 years, leading to the diagnosis of clinically isolated syndrome. The third case is a 30-year-old woman with subacute onset of dysarthria and hemiparesis. She had two BCS lesions along with other demyelinating lesions in the juxtacortical and periventricular regions, cerebellar peduncles, and spinal cord, fulfilling dissemination in time and space. Her neurological deficits resolved after pulse therapy, and she received long-term disease modifying therapy for multiple sclerosis. This study underscores the diverse neuroimaging and clinical presentations of patients with TD lesions, and emphasizes the importance of clinical vigilance regarding this rare condition.


Molecular analysis of antigen recognition by insulin-specific T-cell hybridomas from B6 wild-type and bm12 mutant mice.
Molecular analysis of the heterodimeric T-cell antigen receptor of insulin-specific class II-restricted T-cell hybridomas (THys) derived from C57BL/6 (B6) wild-type and B6.C-H-2bm12 (bm12) mutant mice revealed that such T cells use a diverse V gene repertoire. Analysis of three THys that use related V genes, however, showed a number of novel features. Two THys that share major histocompatibility complex restriction use V alpha genes that are 98.6% homologous. Two THys sharing the same antigen fine specificity use a particular germ line V beta D beta J beta combination. A 21-base-pair deletion in the 5' segment of the J beta gene occurs in one THy, suggesting a novel mechanism for generating diversity in T-cell antigen receptor beta genes. The first amino acid encoded by N sequences at the V-D junction is conserved in a pair of T cells which recognize identical antigenic epitopes. The implications of these findings for the structural mechanisms underlying major histocompatibility complex-restricted antigen-specific T-cell recognition are discussed.


Phosphorylation of the C-terminal domain of the Na+/H+ exchanger by Ca2+/calmodulin-dependent protein kinase II.
The Na+/H+ exchanger is a pH-regulatory protein that extrudes one H+ ion in exchange for one Na+ ion when intracellular pH declines. A number of studies have shown phorbol ester stimulation of activity in intact cells, leading to the idea that the exchanger is regulated by protein kinase C-mediated phosphorylation in vivo. cDNA encoding the protein has been cloned, and a recent model suggests a large internal cytoplasmic C-terminal domain that may be a site of regulation of the exchanger [Sardet, Franchi & Pouyssegur (1989) Cell 56, 271-280]. We examined this region of the protein using a rabbit cardiac Na+/H+ exchanger cDNA clone. cDNA of the Na+/H+ exchanger, coding for the C-terminal 178 amino acid residues, was cloned into the expression vector pEX-1 and expressed as a fusion protein with beta-galactosidase. The fusion protein reacted with an antibody produced against a synthetic peptide of the C-terminal 13 amino acid residues of the Na+/H+ exchanger, confirming the identity of the expressed protein. Control and experimental pEX-1-Na+/H+ exchanger protein was purified on a p-aminophenyl beta-D-thiogalactopyranoside-agarose column. Purified Ca2+/calmodulin-dependent protein kinase II readily phosphorylated the Na+/H+ exchanger protein in a Ca(2+)- and calmodulin-dependent manner in vitro, but this region of the protein was not a substrate for purified protein kinase C or for the catalytic subunit of cyclic AMP-dependent protein kinase. Control-expressed beta-galactosidase was phosphorylated to a maximal level of 0.77 +/- 0.17 mol of Pi/mol (mean +/- S.E.M., n = 6) whereas the fusion protein was phosphorylated to a maximal level of 4.09 +/- 0.39 mol of Pi/mol (n = 6), suggesting one site of phosphorylation in beta-galactosidase and three in the C-terminal domain of the Na+/H+ exchanger. Examination of the deduced amino acid sequence of this part of the exchanger reveals three consensus sequences for Ca2+/calmodulin-dependent protein kinase II. These results suggest that the exchanger may be directly regulated in vivo by calmodulin-dependent protein kinase II but not by protein kinase C or cyclic AMP-dependent protein kinase.


New programme of antenatal care in general practice.
The conclusions from recent analyses of the clinical worth of routine antenatal attendances have been used in the setting of a modern primary health care team. As a result the number of times a low risk nulliparous woman is seen by her general practitioner has been reduced from 15 to eight and a low risk multiparous woman from 15 to six. The number of consultations with a midwife has also been considerably reduced. The time saved is used in longer, more structured consultations and for more intensive care of high risk, usually socially deprived, women. Despite these reductions in consultations organised, well recorded care of this type renders antenatal attendances at a hospital virtually unnecessary for low risk women.


In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure.
Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. Using circular smooth muscle strips obtained from 8 mature horses, increasing concentrations of MNTX were added to tissue baths in the range of 1 x 10(-9) to 1 x 10(-5) mol/l, and contractile responses were recorded for 3 mins. Data were analysed using a repeated measures ANOVA to determine whether there was a significant drug effect compared to baseline activity. Data were analysed between the jejunum and pelvic flexure using a Mann-Whitney U test. Statistical significance was established as P < 0.05. The administration of MNTX significantly increased the contractile frequency and amplitude at all concentrations relative to baseline (P < 0.0001) for the jejunum. The response was greatest at 1 x 10(-7) mol/l (P = 0.0005), with a mean difference from baseline of 115.12 g/cm2. The highest concentration evaluated (1 x 10(-5) mol/l) had a mean contractile strength of 69.76 g/cm2, which was significantly greater than baseline activity (P = 0.04). A significant increase in contractile activity for the colon was detected at 3 x 10(-7) mol/l and all subsequent concentrations (P < 0.04). Unlike the jejunum, the contractile activity of the pelvic flexure increased progressively with the addition of each subsequent concentration. N-methylnaltrexone has a direct effect on circular smooth muscle of the equine jejunum and pelvic flexure resulting in an increase in contractile activity. N-methylnaltrexone could potentially be used in conjunction with morphine to provide potent and effective analgesia without compromising intestinal function. Further in vivo investigations are required to determine whether this agent antagonises morphine's effect on motility.


[Breastfeeding knowledge among post-partum women enrolled in a prenatal care program].
The purpose of this study was to evaluate knowledge of breastfeeding issues among post-partum women who had participated in a prenatal program at the Rio de Janeiro Federal University (UFRJ) Maternity Teaching Hospital. The sample totaled 135 post-partum women who answered a structured questionnaire with objective questions about practical and theoretical aspects of breastfeeding. The women had begun prenatal care at the 16th week of gestation on average, with an average of 8 medical consultations. Some 53.3% stated having received information about breastfeeding during prenatal care, and 22.2% stated that the information they remembered the best was that they should breastfeed for the first 6 months. Regarding the best moment for the first feeding, 50.4% identified it as immediately after delivery. Some 47.4% said breastfeeding protects the child from diseases. Thus, although the mothers demonstrated basic knowledge about breastfeeding, issues like the best moment for the first feeding, the importance of colostrum, and nutritional aspects for nursing mothers require further clarification during prenatal care and the immediate post-partum period.


Design of interpenetrating chitosan and poly(ethylene glycol) sponges for potential drug delivery applications.
Semi-interpenetrating chitosan (CS)/poly(ethylene glycol) (PEG) sponges were designed by crosslinking PEG in the CS matrix via nucleophilic thiol-yne addition. This reaction does not require the use of any potentially cytotoxic catalytic species and offers possibilities to prepare materials with tunable properties. The molecular structure of the sponges was analyzed by FTIR spectroscopy, which provided evidence of intermolecular interactions between PEG and CS, and the presence of a cross-linked PEG network in the CS matrix. The crosslinked CS/PEG sponges displayed a structure with large interconnected pores (tens of micrometers) as demonstrated by scanning electron miscoscopy, in comparison to blended materials with irregular and smaller pores. The crosslinked sponges also exhibited improved mechanical properties (higher Young's modulus) and stability at physiological pH. All together, these interesting properties open the way for the application of this biomaterial in topical drug delivery.


Otoplasty with an unusual cartilage scoring approach.
An ideal otoplasty procedure should minimise the possible risk of severe complications of otoplasty and provide a good aesthetic outcome; however, there is no standart technique to be applied to all types of auricular deformities in different populations. The aim of this study was to present an otoplasty technique with posterior approach in which small incomplete cartilage incisions and suture fixations were used to form the auricle without a need for anterior skin incision and dissection. This study involved 42 patients who had bilateral prominent ears with unfurled antihelixes associated with or without conchal excess. The otoplasty procedure mainly consisted of a posterior skin excision, incomplete cartilage incisions in the shape of greater mark, ">", mattress sutures of the posterior cartilage, earlobe correction, and conchal reduction if necessary. This otoplasty technique consists of easy, simple, and rapid surgical steps without a need for anterior skin dissection and cartilage scoring, so it has a low rate of complications in both early and late postoperative periods. Follow-up time of patients ranged from 1-9 years, with an average of 3 years. No major complications such as haematomas, chondritis, wound infection, skin necrosis, asymmetry, recurrence, hypertrophic scars, granulomas, or irregularities developed in the early and late postoperative periods. A good symmetry and natural appearence were achieved with this otoplasty technique. Patients were satisfied with the results. All over complication rate in the postoperative period was 7%. The presented technique overcomes the drawbacks of anterior skin dissection and anterior scoring, and minimises the risk of severe complications such as anterior skin necrosis, cartilage necrosis or destruction, and ear irregularities. It also reduces the operation time, swelling, bruising, and possibility of suture extrusion and recurrence.


Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy.
Dominant mutations in COL6A1, COL6A2, and COL6A3, the three genes encoding collagen type VI, a ubiquitous extracellular matrix protein, are associated with Bethlem myopathy (BM) and Ullrich scleroatonic muscular dystrophy. The authors devised a method to screen the entire coding sequence of the three genes by reverse transcriptase-PCR amplification of total RNA from skin fibroblasts and direct sequencing of the resulting 25 overlapping cDNA fragments covering 107 exons. Four splicing and four missense mutations were identified in 16 patients with BM, six of which are novel mutations in COL6A1. Both common and private mutations are localized in the alpha1 (VI) chain between the regions corresponding to the 3' end of the NH2-globular domain and the 5' end of the triple helix, encoded by exons 3 through 14. The clustering of the mutations in a relatively narrow area of the three collagen type VI chains in patients with Bethlem myopathy (BM) suggests that mutations in different regions could result in different phenotypes or in no phenotype at all. Moreover, the detection of mutations in only 60% of the patients suggests the existence of at least another gene associated with BM. The authors propose the direct sequencing of COL6 cDNAs as the first mutation screening analysis in BM, given the high number of exon-skipping events.


Global convergence of delayed dynamical systems.
We discuss some delayed dynamical systems, investigating their stability and convergence in a critical case. To ensure the stability, the coefficients of the dynamical system must satisfy some inequalities. In most existing literatures, the restrictions on the coefficients are strict inequalities. The tough question is what will happen in the case (critical case) the strict inequalities are replaced by nonstrict inequalities (i.e., "<" is replaced by "=/<"). The purpose of the paper is to discuss this critical case and give an affirmative answer in the case that the activation functions are hyperbolic tangent.


Group IIA secreted phospholipase A2 controls skin carcinogenesis and psoriasis by shaping the gut microbiota.
Besides promoting inflammation by mobilizing lipid mediators, group IIA secreted phospholipase A2 (sPLA2-IIA) prevents bacterial infection by degrading bacterial membranes. Here, we show that, despite the restricted intestinal expression of sPLA2-IIA in BALB/c mice, its genetic deletion leads to amelioration of cancer and exacerbation of psoriasis in distal skin. Intestinal expression of sPLA2-IIA is reduced after treatment with antibiotics or under germ-free conditions, suggesting its upregulation by gut microbiota. Metagenome, transcriptome, and metabolome analyses have revealed that sPLA2-IIA deficiency alters the gut microbiota, accompanied by notable changes in the intestinal expression of genes related to immunity and metabolism, as well as in the levels of various blood metabolites and fecal bacterial lipids, suggesting that sPLA2-IIA contributes to shaping of the gut microbiota. The skin phenotypes in Pla2g2a-/- mice are lost (a) when they are cohoused with littermate WT mice, resulting in the mixing of the microbiota between the genotypes, or (b) when they are housed in a more stringent pathogen-free facility, where Pla2g2a expression in WT mice is low and the gut microbial compositions in both genotypes are nearly identical. Thus, our results highlight a potentially new aspect of sPLA2-IIA as a modulator of gut microbiota, perturbation of which affects distal skin responses.


Histological Remission in Ulcerative Colitis in Deep Remission under Treatment with Adalimumab.
Histological remission (HR) has been recently demonstrated as the last therapeutic goal in ulcerative colitis (UC), but it is unknown whether and how it may occur. Our aim was to assess the histology during the follow-up of an UC population in deep remission under treatment with adalimumab (ADA). We performed a retrospective study on 22 UC patients who were in deep remission and followed-up while receiving therapy with ADA. Colonoscopy in those patients was performed every year. Four-quadrant biopsies every 10 cm were obtained during each colonoscopy and assessed by hematoxylin and eosin stain. Histological activity was classified using the Geboes scale. A total of 22 patients were enrolled in the study. The mean follow-up of those patients was 28±7 months, and 2,592 biopsy specimens in total were taken during 108 colonoscopies performed during the follow-up. At the beginning of the follow-up, histological inflammation was found in 15/22 (68.2%) of patients in deep remissio while receiving maintenance ADA therapy, 8/22 (36.4%) of them with Geboes score ≥3.1. At the end of the follow-up, when patients were still in deep remission while receiving maintenance ADA therapy, only 4 patients (18.2%) had at least one biopsy specimen with evidence of any histological inflammation during the follow-up; only two patients (9.1%) had Geboes score ≥3.1. Our study shows for the first time that UC patients in deep remission under ADA may reach HR, but it seems slower than other clinical or endoscopic goals.


Rapid detection and quantitation of human cytomegalovirus in urine through DNA hybridization.
We detected cytomegalovirus DNA in clinical urine specimens after immobilization on nitrocellulose filters and hybridization with a radioactively labeled, cloned fragment of cytomegalovirus DNA. We accomplished the specific detection and quantitation of viral DNA within 24 hours with 39 urine specimens from nine patients with cytomegalovirus viruria, mostly at a tissue-culture infective titer of 10(3) per milliliter or higher. None of 57 urine specimens from 21 patients that were culture-negative for cytomegalovirus gave false-positive results. Analysis of specimens from patients with cytomegalovirus viruria showed a correlation of the infective titer with the intensity of DNA hybridization (r = 0.77). Hybridization of sequential urine specimens from a patient undergoing treatment with interferon for cytomegalovirus retinitis revealed quantitative variations in hybridizable viral DNA over a period that correlated with clinical findings. This assay can be useful in the selection of patients for antiviral therapy and for the assessment of its efficacy.


Soil moisture variations affect short-term plant-microbial competition for ammonium, glycine, and glutamate.
We tested whether the presence of plant roots would impair the uptake of ammonium ([Formula: see text]), glycine, and glutamate by microorganisms in a deciduous forest soil exposed to constant or variable moisture in a short-term (24-h) experiment. The uptake of (15)NH4 and dual labeled amino acids by the grass Festuca gigantea L. and soil microorganisms was determined in planted and unplanted soils maintained at 60% WHC (water holding capacity) or subject to drying and rewetting. The experiment used a design by which competition was tested in soils that were primed by plant roots to the same extent in the planted and unplanted treatments. Festuca gigantea had no effect on microbial N uptake in the constant moist soil, but its presence doubled the microbial [Formula: see text] uptake in the dried and rewetted soil compared with the constant moist. The drying and rewetting reduced by half or more the [Formula: see text] uptake by F. gigantea, despite more than 60% increase in the soil concentration of [Formula: see text]. At the same time, the amino acid and [Formula: see text]-N became equally valued in the plant uptake, suggesting that plants used amino acids to compensate for the lower [Formula: see text] acquisition. Our results demonstrate the flexibility in plant-microbial use of different N sources in response to soil moisture fluctuations and emphasize the importance of including transient soil conditions in experiments on resource competition between plants and soil microorganisms. Competition between plants and microorganisms for N is demonstrated by a combination of removal of one of the potential competitors, the plant, and subsequent observations of the uptake of N in the organisms in soils that differ only in the physical presence and absence of the plant during a short assay. Those conditions are necessary to unequivocally test for competition.


[When should one operate for asymptomatic chronic aortic insufficiency?].
In the presence of symptomatic aortic insufficiency, the indication for surgery is accepted. On the other hand, when the patient is asymptomatic, there is hesitation between intervening too early because of the operative risk and complications of valvular prostheses, and operating too late because of the progressive spontaneous risk of aortic parietal complications, sudden death or irreversible left ventricular dysfunction. Before any discussion, it is logical to verify the asymptomatic character of the patient with a stress test. On knowing the severity of the aortic insufficiency, which is usually confirmed by Doppler echocardiography, the decision is based partly on the left ventricular effects and the ascending aortic diameters, and partly on the operative risk modified by age and associated pathologies. In this article, drawing on the data in the literature we set out to discuss the operative indications in asymptomatic chronic aortic insufficiency.


Stress under modernization in indigenous populations of Siberia.
Arterial blood pressure and serum blood glucose concentration, and the level of anxiety, as determined by the Spielberger test, as physical and psychological markers of stress under "modernization", were studied in groups of native Siberians: the Khanty and the Mansi. The fraction of respondents with a high level of anxiety is 64% of the total sample. The average values of systolic and diastolic blood pressure are higher among natives living in large than in small "national" settlements (p<0.05). The arterial blood pressure of town dwellers is even higher. The same patterns are seen in the blood serum glucose concentrations in female samples. The average arterial blood pressure (in males and females) and the blood serum glucose concentration (in females) increases as people diverge from "traditional" lifestyles. The results demonstrate that "modernization" and urbanization have a serious stressing influence on the aborigines of North Siberia.


Cell-cell adhesion proteins in melanocytic pilomatrix carcinoma.
Tumors of the matrix of rigid structures include matrical tumors of the hairs, nails, and teeth. These tumors share similar phenotypical and signaling features. Although benign matrical hair tumors are among the most common of these tumors, hair matrix tumors containing pigmented melanocytes are very rare. The malignant variant called melanocytic pilomatrix carcinoma contains benign colonizing dendritic melanocytes admixed with the carcinomatous follicular matrical cells.We studied the expression of cadherins and β-catenin in melanocytic pilomatrix carcinoma because cadherin/catenin-dependent cell-cell adhesion and signals play a critical role in the development of hair and hair tumors. We examined the expression of E- and P-cadherin and the multifunctional protein β-catenin in two cases of melanocytic pilomatrix carcinoma by immunohistochemistry. E- and P-cadherin are expressed at the cell membrane. In contrast, β-catenin is distributed uniformly in the nucleus and cytoplasm of all tumor cells. The diffuse nuclear and cytoplasmic β-catenin expression found in melanocytic pilomatrix carcinomas is indicative of transcriptional activation and β-catenin-induced cell transformation.This is the first report of cadherin/catenin expression in melanocytic pilomatrix carcinoma. Although the study is limited by the number of these rare tumors, the data add information for the understanding of disease mechanisms in hair matrical tumors. Matrical tumors of the hairs share phenotypical features with other matrical tumors and show nuclear translocation of β-catenin, suggesting a transcriptional activating rather than a cellcell adhesion function.


Truncated semenogelin I binds zinc and is cleaved by prostate-specific antigen.
Semenogelins I and II are major coagulum-forming proteins in semen, and they are secreted mainly by the seminal vesicles. These proteins bind Zn(2+) and act as substrates for prostate-specific antigen and transglutaminase. A variant semenogelin I lacking 60 amino acids has been described that occurs in different populations with an allele frequency of 1%-3%. To better understand the function of the semenogelins in vivo, our aim was to characterize the properties of the variant form and compare with the wild type. Recombinant proteins were synthesized in insect cells. Binding of Zn(2+) was studied by titration of metal ions in the presence of a zinc (II) fluorophore chelator. SDS-PAGE was used to visualize the results of cleavage by prostate-specific antigen and cross-linking with transglutaminase. We found that the truncated and wild-type semenogelin molecules had similar Zn(2+)-binding properties (ie, a stoichiometry of at least 9-10 mol per mol of protein and an average dissociation constant of 5 mumol/L per site), and they showed also similar susceptibility for degradation by prostate-specific antigen. Furthermore, like the wild-type form, the truncated semenogelin I was able to serve as a substrate for transglutaminase. These findings imply that the studied characteristics do not depend on a well-defined tertiary structure, or that the deletion has no major effect on the structure responsible for these features.


Circadian clustering of spontaneous epileptic seizures emerges after pilocarpine-induced status epilepticus.
Seizures in mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis are thought to develop with various latency intervals after an initial transient brain insult. To study seizure dynamics after an initial transient precipitating insult in a systematic fashion, we utilized continuous video-electroencephalography (EEG) monitoring after the induction of status epilepticus (SE) in a mouse MTLE model. Continuous 24/7 video/telemetric hippocampal EEG recordings in the systemic pilocarpine MTLE mouse model. After SE, we observed emerging seizures interfering with the circadian EEG rhythms. The physiologic circadian EEG pattern of mice was transiently suppressed for 2.9 (mean) ± (SEM) 0.5 days after SE. This period was accompanied predominately by nonconvulsive seizure activity, followed by convulsive seizures at later stages. After the circadian rhythm was restored, spontaneous generalized seizures occurred mainly in a clustered manner in a narrow time window between 4 and 7 p.m. (light cycle 7 a.m./7 p.m.). Moreover, we demonstrate that depth-electrode implantation surgery transiently disturbs the physiologic EEG circadian cycle; variation of the time point of SE induction after electrode insertion surgery revealed a substantial impact on the epilepsy phenotype, which was more severe when SE occurred after postsurgical reappearance of EEG circadian cycling. These data have several experimental and pathophysiologic implications. The impact of depth-electrode surgery on the phenotype has to be tightly controlled. In mice monitored after pilocarpine-induced SE, the "epileptogenesis" period is characterized by the dynamics of epileptiform activity toward behavioral recurrent seizure patterns. The striking clustering of spontaneous seizures at the transition from sleep to activity stages of mice has to be taken into account for future studies on the model. Improving our understanding of the molecular mechanisms that determine the circadian dynamics of seizure threshold remains an intriguing task for the future.


Kinase II-dependent formation of angiotensins II and III in the hepatic circulation.
Experiments were performed in 14 pentobarbital-anesthetized dogs to 1) determine if the hepatic arterial vasoconstrictor effects of [des-Asp1]angiotensin I [( des-Asp1]ANG I) were due to its local conversion to angiotensin III (ANG III) and 2) to evaluate the magnitude of conversion of ANG I to angiotensin II (ANG II) and of [des-Asp1]ANG I to ANG III in the hepatic arterial vascular bed. Graded doses of these peptide agonists were administered as bolus injections directly into the hepatic artery; hepatic arterial blood flow was measured with an electromagnetic flow probe. Dose-response relationships were determined before and during the inhibition of kinase II activity with captopril (2-D-methyl-3-mercaptopropanoyl-L-proline) and antagonism of angiotensin receptor sites with [Ile7]angiotensin III [( Ile7]ANG III). ANG I and [des-Asp1]ANG I were equipotent at all doses tested, as were ANG II and III. At all doses tested, ANG II and III were approximately three times more potent than ANG I and [des-Asp1]-ANG I. Captopril attenuated the vasoconstrictor responses to ANG I and [des-Asp1]ANG I only, whereas [Ile7]ANG III inhibited the responses to all four angiotensin peptides. These data indicate that the hepatic arterial vasoconstrictor responses to [des-Asp1]ANG I were due to the intrahepatic formation of ANG III. The extent of intrahepatic conversion of [des-Asp1]-ANG I to ANG III that occurred in one transit through the hepatic arterial vascular bed was estimated to be 33%, which was similar to the estimated 38% conversion of ANG I to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cystic tumors in the retrorectal space. Do these two cases have something in common?].
Cystic lesions in the retrorectal or presacral space present a broad differential diagnosis. Rare but typical lesions at this site are those related to embryonic development, which are the most frequent presacral congenital lesions in adults. Amongst these tumors, epidermoid cysts and cystic hamartomas are the most common lesions. Cystic masses, which are asymptomatic in approximately 50% of the cases at diagnosis, may show complications such as infection or malignant degeneration. Initial diagnosis is based on imaging techniques although definite lesion characterization, essential due to their malignancy risk, is given by the pathological analysis of the surgical piece.


Behavioural traits modulate the use of heterospecific social information for nest site selection: experimental evidence from a wild bird population.
The use of social information for making decisions is common but can be constrained by behavioural traits via, for example, the ability to gather information. Such constrained information use has been described in foraging habitat selection; yet it remains unexplored in the breeding habitat selection context, despite potentially strong fitness consequences. We experimentally tested whether three behavioural traits (aggressiveness, boldness and neophobia) affected the use of heterospecific social information for nest site selection in wild collared flycatchers Ficedula albicollis. Flycatchers have previously been found to copy or reject an artificial apparent preference of tits (their main competitors) for a nest site feature: they preferred nest-boxes with the same or a different feature, depending on tit early reproductive investment. Here, we confirmed this result and showed that shy individuals and less aggressive old males (i.e. 2 years old or older) copied tit apparent preference, while more aggressive old males rejected the tit preference. Aggressiveness and boldness may allow males to access more information sources or affect males' interactions with dominant tits when selecting a nest site. Our study highlights the links between variation in behaviours and social information use for breeding habitat selection and calls for further work to explore underlying mechanisms.


A system for non-invasively measuring blood pressure on a treadmill.
Measurement of signal to artifact ratio yielded optimal frequencies for a Korotkoff-based automatic system for measuring blood pressure on a treadmill. Maximal Korotkoff sounds occurred just above the crease of the elbow over the brachial artery. Output of a piezoelectric microphone and charge amplifier was measured during treadmill exercise for frequency bands from 8 to 57 Hz. An automatic system filtered output from 40 to 45 Hz, rectified it, then compared it to a threshold that had fixed and exponentially decaying components. For five subjects, the system decisions of systolic and diastolic pressures compared well with those of two observers using stethoscopes. The system shows promise for improved measurements of blood pressure during treadmill exercise.


ARMA Modeling of Time Series.
A method for efficiently generating a rational model of a wide-sense stationary time series is presented. In this method the autoregressive parameters associated with an ARMA model consisting of q zeros and p poles are optimally chosen with the selection being based on a finite set of time series observations. This selection is made so that a set of Yule-Walker equation approximations are ``best'' satisfied. The resultant autoregressive parameter estimates have the desired statistical feature of being unbiased and consistent. This estimation method has been found to provide a modeling performance which typically equals or exceeds that of contemporary alternatives. Moreover, this method is amenable to a computationally efficient adaptive solution procedure. The autoregressive parameters characterizing the resultant ARMA model estimate can serve the role of decision variables in pattern classification schemes. For example, these parameters can be utilized in determining whether or not a member(s) of a given signal class is contained within a noise corrupted measurement signal. This approach has been found to be particularly effective in Doppler radar and array processing applications in which one is looking for the presence of spectral lines (i.e., sinusoids) in the measurement signal.


Thirty- Versus Ten-Day Diazepam Treatment for Alcohol Detoxification and a Comparison of Drinking Patterns, Craving, and Anxiety for up to 12 Weeks: A "Proof-of-Concept" Open-Label Randomized Controlled Trial.
The aim of this study was to evaluate whether a prolonged detoxification treatment could decrease the relapse rate at 3 months after alcohol cessation in alcohol-dependent individuals through decreasing the levels of postdetoxification craving and anxiety. Twenty-six adult patients with alcohol dependence (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) who began an outpatient alcohol cessation program with an initial drinking goal of abstinence were enrolled in a 3-month, parallel, randomized (1:1 ratio), controlled, open-label, pilot trial. Participants were randomized to receive a detoxification treatment of diazepam with a duration of 30 (n = 12) or 10 days (n = 14). All participants received BRENDA-based psychotherapy during follow-up. No significant between-group difference in relapse to any drinking was found at 3 months (P = 0.20). However, relapse to any heavy drinking at 3 months and regular drinking or heavy drinking during follow-up were significantly lower in the 30-day diazepam group (P = 0.009, P = 0.049, and P = 0.004, respectively). These differences were corroborated by significant differences in the alcohol-specific biological marker carbohydrate deficient transferrin at 3 months. Participants in the 30-day diazepam group also displayed significantly lower scores for alcohol craving (P = 0.007), self-reported anxiety (P = 0.024), and clinician-assessed anxiety (P = 0.002) throughout the follow-up. No serious adverse event was reported during the study. This study provides an evidence-based rationale for a double-blind, randomized, placebo-controlled trial to confirm the efficacy of such a procedure on short-term and mid-/long-term drinking outcomes after alcohol cessation in alcohol-dependent individuals.


Case report: unusual CT appearances in a case of Budd-Chiari syndrome.
We describe a case of Budd-Chiari Syndrome due to hepatic venous blockage in which there were multiple space-occupying lesions on CT simulating tumour deposits. Ultrasound directed liver biopsy and laparoscopy proved these to be areas of haemorrhagic necrosis consistent with Budd-Chiari Syndrome without any evidence of malignancy. The CT finding of multiple large focal non-enhancing areas in liver does not always indicate tumour deposits in a patient suspected to have Budd-Chiari Syndrome.


Immune response of post-transplant peripheral lymphocytes against the patient pre-B cell line, NAGL-1.
We have established a pre-B acute lymphoblastic leukemia (ALL) cell line, NAGL-1, from the bone marrow of a patient diagnosed with pre-B ALL. The patient has been disease-free for the 4 years since allogeneic bone marrow transplantation from her HLA-genotypically identical sister. NAGL-1 showed a pre-B cell phenotype (CD19+, CD10+, c mu+, s mu-) mostly identical to freshly isolated leukemic cells from the patient. This cell line strongly expressed HLA class I and HLA-DR molecules, as well as the costimulatory molecules CD54, CD40, and CD86. Cytotoxic T-lymphocyte (CTL) lines were generated by stimulating the donor-derived peripheral blood mononuclear cells with either irradiated leukemic cells or NAGL-1. Both CTL lines showed specific lysis against NAGL-1 in 51Cr release assays. Lytic activity was partially inhibited by anti-CD8 and anti-HLA class I monoclonal antibodies. Treatment of NAGL-1 with TNF-alpha increased its susceptibility to the CTL line. One CD8+ T cell clone derived from the CTL line killed both the patient phytohemagglutinin (PHA) blasts and NAGL-1 but not the donor PHA blasts, suggesting that the clone recognized the patient-specific minor antigen presented on both PHA blasts and NAGL-1. Utilization of leukemic cell lines could be a useful model for the development of CTL lines and clones for immunological study and potential immunotherapy.


A primary method for determination of optical parameters of turbid samples and application to intralipid between 550 and 1630 nm.
The lack of a primary method for determination of optical parameters remains a significant barrier in optical study of turbid media. We present a complete system of experimental setups and Monte Carlo modeling tools for fast and accurate solution of the inverse problem from the measured signals of homogeneous turbid samples. The calibration of the instrument and validation of the Monte Carlo modeling have been carried out to ensure the accuracy of the inverse solution. We applied this method to determine the optical parameters of turbid media of 10% intralipid between 550 and 940 nm and 20% intralipid between 550 and 1630 nm.


Association of estrogen receptor-alpha and vitamin D receptor genotypes with therapeutic response to calcium in postmenopausal Chinese women.
To investigate the correlation between calcium treatment in postmenopausal women and estrogen receptor-alpha (ER-alpha) Xba I and Pvu II genotype and vitamin D receptor (VDR) Apa I genotype. One hundred fifteen postmenopausal Chinese women of Han population were enrolled and treated with calcichew-D3 (1000 mg calcium and 400 U vitamin D3) daily for 1 year. At entry and after 1 year treatment, the bone mineral density (BMD), serum and urinary bone turnover biochemical markers were evaluated. ER-alpha and VDR genotype were analyzed using PCR-restriction fragment length polymorphism. After 1 year of calcium supplementation, a significant increase of BMD and a marked reduction in serum ALP and PTH levels, and a significant increase of serum 25-(OH) vitamin D level were observed (P<0.01 or P<0.05). At entry and after 1 year of treatment, no significant association was found between Xba I, Pvu II, and Apa I genotypes and BMD in L1-4, Neck, and Troch, and all bone turnover marker levels. However, the percentage of change (median, QR) in Neck BMD was significantly different in homozygous XX [-4.14 (from -6.54 to -1.34)] in comparison with Xx [1.72 (from -1.12 to 3.20)] (P<0.001) or xx [1.22 (from -1.74 to 3.06)] Xba I ER-alpha genotype (P=0.001). Women with ER-alpha Xba I genotype XX may have a higher risk of relatively fast bone mass loss in femoral neck after menopause and that they may have a poor responsiveness to calcium supplementation. The changes in BMD are not associated with ER-alpha Pvu II genotype and VDR Apa I genotype after 1 year of calcium supplementation.


Section for Residents and Fellows-in-Training Leaders: Where Are They Now?
The purpose of this study was to examine the experiences of prior governing council (GC) members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Section for Residents and Fellows-in-Training (SRF) and assess the impact of early Academy involvement. A survey was conducted via email on all prior AAO-HNS SRF GC members. The AAO-HNS SRF has elected 52 GC members since its 2003 inception. Each member served an average of 1.5 year-long terms. The mean time since completion of training is 4.1 years. A subspecialty fellowship was pursued in 86%. Fifty-seven percent practice in academic settings, with 3 members advancing to subspecialty division director within their department. More than half (58%) have served on an AAO-HNS committee, and most are frequent attendees of the annual meeting. All prior members felt involvement in the SRF GC was beneficial, enabling them to gain leadership skills and deeper understanding of the specialty.


Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.
The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology. In this article, some of the reasons for these contentions are discussed. Pragmatic recommendations for operational thresholds, ie, blood glucose levels at which clinical interventions should be considered, are offered in light of current knowledge to aid health care providers in neonatal medicine. Future areas of research to resolve some of these issues are also presented.


[Surgical treatment of spontaneous and traumatic pneumothorax].
The ten-year experience of the regional hospital thoracic department in treatment of 723 patients with spontaneous pneumothorax and 678 injured persons, suffering complicated thoracic trauma, was summarizd. The tactic and methods of treatment of such patients, using modern technologies and endoscopic operations, was depicted. Comparative analysis of the different methods efficacy, their results, advantages and faults estimation were conducted. Recommendations for application of every method of treatment in various clinical situations were adduced.


Complications of lateral plating in the minimally invasive lateral transpsoas approach.
The aim of this study was to review the authors' experience with 101 cases over the past 3 years with minimally invasive lateral interbody fusion using a lateral plate. Their main goal was to specifically look for hardware-associated complications. Three cases of hardware failure and 3 cases of vertebral body (VB) fractures associated with lateral plate placement are reported. The authors also review the literature pertaining to lateral plates and related complications. This study is a retrospective review of a database of patients who underwent minimally invasive lateral interbody fusion in the thoracolumbar spine during a 3-year period. Six complications were identified, resulting in an incidence of 5.9%. Three hardware failures, 2 coronal plane VB fractures, and 1 lateral VB fracture were identified. All complications occurred in multilevel cases. All cases presented with recurrent back pain except one, which was identified incidentally. Minimally invasive lateral interbody fusion is a safe and direct technique that is practical, especially when trying to avoid other approaches for hardware insertion, and it also avoids the complications associated with other types of instrumentation such as pedicle screws. Careful consideration during patient selection and during the operation will aid in the avoidance of complications.


The signal transducer and activator of transcription 5B gene polymorphism contributes to the cholesterol metabolism in Japanese children with growth hormone deficiency.
GH plays a significant role in the lipid metabolism. In this study, we focused on the JAK2 - signal transducer and activator of the transcription 5 (STAT5) pathway, which transmit the signals from the GH receptor, and selected the STAT5A/B gene as a candidate for the regulation of lipid metabolism in GH deficiency (GHD). The study population comprised 83 children with idiopathic GHD. The serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and the non-HDL cholesterol (non-HDL-C) levels were monitored before and at 3, 6, 9 and 12 months after starting GH treatment. The height, weight, body mass index, and serum insulin-like growth factor-I (IGF-I) level were also measured before and 12 months after starting the GH treatment. For the genetic analysis of the STAT5A/B gene, five tag SNPs were selected using the tag SNP picker programme on the homepage of the HapMap project. The evaluation of promoter activity of the -44816A/G SNP in the STAT5B gene was performed by a luciferase assay in vitro. The TC and non-HDL-C levels were gradually decreased during the GH treatment. Five tag SNPs (rs4029774, rs6503691, rs9900213, rs16967637 and rs2272087) were picked up for the STAT5A/B gene, and the genetic study demonstrated that the paediatric GHD patients who were heterozygotes or homozygotes of minor alleles of the analysed SNPs in the same block of the STAT5B gene showed significantly higher serum TC or non-HDL-C levels both before and after GH treatment for 12 months. Most of the SNPs also demonstrated significant differences among genotypes in the decreases in serum TC or non-HDL-C levels during the 12 months of GH treatment. A luciferase assay showed that the -44816A/G SNP (rs4029774) in the STAT5B gene functionally affected the expression level in vitro. These results indicate that STAT5B may therefore play a role in regulating the cholesterol metabolism in children with GHD.


Serologic evidence of chicken infectious anemia in commercial chicken flocks in southwest Nigeria.
Sera samples from seven poultry farms in southwest Nigeria consisting of 7 broiler, 10 pullet, 1 layer, 1 cockerel, and 1 broiler breeder flocks were tested for the presence of chicken infectious anemia virus (CIAV) antibodies using a commercial enzyme-linked immunosorbent assay kit. Eleven of the 20 flocks (55%) and six out of seven (86%) farms were positive for CIAV antibodies. The seroprevalence largely depended on the age of the flocks. Seroprevalence was higher within the older pullet and layer flocks (83%-100%) than in the younger broiler flocks (0%-83%). In essence, all flocks older than 6 to 8 wk became infected. This is the first report of serologic evidence of CIAV in Subsaharan Africa. Since Southwest Nigeria is the main port of entry of imported chicken and the hub of major poultry breeders, the disease can probably be found throughout the country and beyond. Further studies are necessary to assess economic losses due to CIAV and the cost benefit of countermeasures.


Localization of tubby-like protein 1 in developing and adult human retinas.
To localize tubby-like protein 1 (TULP1) in developing and adult human retinas. TULP1 was localized by immunofluorescence microscopy in human retinas, aged 8.4 fetal weeks to adult. TULP1-positive cells were identified by double labeling with antibodies specific for cones, rods, and astrocytes. In adult retinas, anti-TULP1 labels cone and rod inner segments, somata, and synapses; outer segments are TULP1-negative. A few inner nuclear and ganglion cells are weakly TULP1-positive. In fetal retinas, cells at the outer retinal border are TULP1-positive at 8.4 weeks. At 11 weeks, the differentiating central cones are strongly TULP1-reactive and some are positive for blue cone opsin. At 15.4 weeks, all central cones are strongly positive for TULP1 and many are reactive for red/green cone opsin. At 17.4 weeks, central rods are weakly TULP-reactive. In peripheral retina at 15.4 weeks to 1 month after birth, displaced cones in the nerve fiber layer are positive for TULP1, recoverin, and blue cone opsin. Some ganglion cells are weakly reactive for TULP1 at 11 weeks and later, but astrocytes and the optic nerve are TULP1-negative at all ages examined. The finding of TULP1 labeling of cones before they are reactive for blue or red/green cone opsin suggests an important role for TULP1 in development. TULP1 expression in both developing and mature cones and rods is consistent with a primary photoreceptor defect in retinitis pigmentosa (RP) caused by TULP1 mutations. Weak TULP1-immunolabeling of some inner retinal neurons in developing and adult retinas suggests that optic disc changes in patients with RP who have TULP1 mutations may be primary as well as secondary to photoreceptor degeneration.


High dietary omega-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA base adducts in white blood cells of female subjects.
Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal and malonaldehyde, which form promutagenic exocyclic DNA adducts in human cells and may contribute to diet-related cancers. Using ultrasensitive detection methods, analysis of WBC DNA from volunteers in a dietary study revealed that high intake of omega-6 polyunsaturated fatty acids increased malonaldehyde-derived adducts in male and female subjects. In contrast, etheno adducts (1,N6-ethenodeoxyadenosine; 3,N4-ethenodeoxycytidine) were not elevated in males but were, on average, 40 times higher in females, displaying a huge intersubject variation in lipid peroxidation-derived DNA damage. Exocyclic DNA adducts are promising biomarkers for examining the hypothesis of possible links between increased intake of dietary omega-6 polyunsaturated fatty acids, DNA damage, and elevated cancer risk for breast, colon, and prostate.


Cell and molecular anatomy of nicotinic acetylcholine receptor subunits and calcitonin gene-related peptide in the rat vestibular system.
In this report we demonstrate the pattern of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity in the central and peripheral vestibular system of the rat, using a CGRP cRNA probe and a polyclonal CGRP antiserum. We present evidence that somata in all regions of efferent vestibular neurons contain CGRP based on the correspondence between in situ hybridization (mRNA) and immunohistochemistry (mRNA translation product). CGRP immunohistochemistry (CGRPi) and in situ hybridization confirm that CGRPi axons and terminals present in the vestibular neuroepithelium are efferent in origin. Immunoelectron microscopy revealed an extensive innervation of the afferent vestibular pathway by CGRPi terminals that was not limited to the primary afferent chalice, as previously reported by Tanaka et al. (Brain Res 1989;504:31-5). An efferent neuromodulatory role of CGRP can be inferred from the distribution of terminals found on the primary afferent fibers, and type I and type II hair cells. In addition, we present evidence that nicotinic acetylcholine receptor (nAChR) subunit mRNA is expressed by primary afferent cell bodies. On the basis of these data, a hypothetical molecular mechanism of vestibular efferent modulation of the primary afferent pathway is proposed.


Effectiveness of general practice interventions for patients with harmful alcohol consumption.
Harmful alcohol consumption can have severe consequences for both the individual and society. A review of the six published studies on the effectiveness of general practitioner interventions for individuals with harmful alcohol consumption suggests that between five and 10 minutes of advice leads to reductions of alcohol consumption of around 25-35% at follow up six months or one year later. Two of the three studies which failed to demonstrate an intervention effect had inadequate sample sizes and in two of the studies the control group was a comparison group which received minimal advice to reduce alcohol consumption. There was greater evidence for an intervention effect among men than women. The methodological problems of the studies are discussed.


Plant responses to bacterial N-acyl L-homoserine lactones are dependent on enzymatic degradation to L-homoserine.
Many bacteria use quorum sensing (QS) to regulate phenotypes that ultimately benefit the bacterial population at high cell densities. These QS-dependent phenotypes are diverse and can have significant impacts on the bacterial host, including virulence factor production, motility, biofilm formation, bioluminescence, and root nodulation. As bacteria and their eukaryotic hosts have coevolved over millions of years, it is not surprising that certain hosts appear to be able to sense QS signals, potentially allowing them to alter QS outcomes. Recent experiments have established that eukaryotes have marked responses to the N-acyl L-homoserine lactone (AHL) signals used by Gram-negative bacteria for QS, and the responses of plants to AHLs have received considerable scrutiny to date. However, the molecular mechanisms by which plants, and eukaryotes in general, sense bacterial AHLs remain unclear. Herein, we report a systematic analysis of the responses of the model plants Arabidopsis thaliana and Medicago truncatula to a series of native AHLs and byproducts thereof. Our results establish that AHLs can significantly alter seedling growth in an acyl-chain length dependent manner. Based upon A. thaliana knockout studies and in vitro biochemical assays, we conclude that the observed growth effects are dependent upon AHL amidolysis by a plant-derived fatty acid amide hydrolase (FAAH) to yield L-homoserine. The accumulation of l-homoserine appears to encourage plant growth at low concentrations by stimulating transpiration, while higher concentrations inhibit growth by stimulating ethylene production. These results offer new insights into the mechanisms by which plant hosts can respond to QS signals and the potential role of QS in interkingdom associations.


Exosome-mediated quality control: substrate recruitment and molecular activity.
The eukaryotic exosome is a multisubunit complex that is mainly responsible for 3'-5' exonucleolytic degradation of RNAs, both in the nucleus and the cytoplasm. In this review we summarize the recent experiments that have provided information on the organisation, structure and activity of this large assembly. Interestingly, eukaryotic exosomes have been implicated in a large number of RNA degradation pathways including recently discovered RNA quality control mechanisms. A variety of cofactors have been shown to participate in substrate recruitment and/or assist exonucleolytic activities. Despite this avalanche of new results, further analyses will be required to improve our understanding of exosome regulation.


Accuracy of an experimental whole-blood test for detecting reactivation of echinococcal cysts.
Cystic echinococcosis (CE) is a complex disease for which clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. We evaluated the accuracy of a whole-blood stimulation test based on Interleukin (IL)-4 detection in response to Antigen B (AgB) of Echinococcus granulosus sensu lato to discriminate cyst viability and detect cyst reactivation in patients with hepatic CE. Thirty patients with CE3b cysts and 37 patients with spontaneously-inactivated CE4-CE5 cysts were recruited (T0). After enrollment, 5 patients with CE3b cysts received albendazole, resulting in cyst solidification (CE4) in 4/5. Within a two-year follow-up, the whole-blood test was repeated at two time-points, in ≥14 (T1) and in ≥4 (T2) patients per group. IL-4 and a panel of other soluble factors were measured in the stimulated plasma. Baseline IL-4 levels were significantly higher in patients with CE3b compared to those with CE4 cysts (p = 0.006). Test accuracy for CE3b diagnosis had a sensitivity of 33-60% and a specificity of 76-95%, depending on the cut-off applied. Overall, IL-4 levels did not change significantly over time in either group; however, patients within the CE3b group showed a significant decrease of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF at T1 compared to T0 (p≤0.042). Whole-blood IL-4-response to AgB is significantly higher in patients with active compared to inactive CE but apparently not modulated over time after treatment. On the contrary, the levels of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients' follow-up.


The sperm surface localization of the TRP-3/SPE-41 Ca2+ -permeable channel depends on SPE-38 function in Caenorhabditis elegans.
Despite undergoing normal development and acquiring normal morphology and motility, mutations in spe-38 or trp-3/spe-41 cause identical phenotypes in Caenorhabditis elegans-mutant sperm fail to fertilize oocytes despite direct contact. SPE-38 is a novel, four-pass transmembrane protein and TRP-3/SPE-41 is a Ca(2+)-permeable channel. Localization of both of these proteins is confined to the membranous organelles (MOs) in undifferentiated spermatids. In mature spermatozoa, SPE-38 is localized to the pseudopod and TRP-3/SPE-41 is localized to the whole plasma membrane. Here we show that the dynamic redistribution of TRP-3/SPE-41 from MOs to the plasma membrane is dependent on SPE-38. In spe-38 mutant spermatozoa, TRP-3/SPE-41 is trapped within the MOs and fails to reach the cell surface despite MO fusion with the plasma membrane. Split-ubiquitin yeast-two-hybrid analyses revealed that the cell surface localization of TRP-3/SPE-41 is likely regulated by SPE-38 through a direct protein-protein interaction mechanism. We have identified sequences that influence the physical interaction between SPE-38 and TRP-3/SPE-41, and show that these sequences in SPE-38 are required for fertility in transgenic animals. Despite the mislocalization of TRP-3/SPE-41 in spe-38 mutant spermatozoa, ionomycin or thapsigargin induced influx of Ca(2+) remains unperturbed. This work reveals a new paradigm for the regulated surface localization of a Ca(2+)-permeable channel.


MoO2 Nanoclusters Embedded in Hierarchical Nitrogen Doped Carbon Nanoflower as Electrocatalytic Mediators in Aqueous Zinc-Tellurium Batteries: Enhancing Electrochemical Kinetics of Tellurium Redox Reaction.
Aqueous zinc-ion batteries (AZIBs) are considered to be one of the most promising devices for large-scale energy storage systems owing to their high theoretical capacity, environmental friendliness, and safety. However, the ionic intercalation or surface redox mechanisms in conventional cathode materials generally result in unsatisfactory capacities. Conversion-type aqueous zinc-tellurium (Zn-Te) batteries have recently gained widespread attention owing to their high theoretical specific capacities. However, it remains an enormous challenge to improve the slow kinetics of the aqueous Zn-Te batteries. Here, MoO2 nanoclusters embedded in hierarchical nitrogen-doped carbon nanoflower (MoO2 /NC) hosts are successfully synthesized and loaded with Te in aqueous Zn-Te batteries. Benefitting from the highly dispersed MoO2 nanoclusters and hierarchical nanoflower structure with a large specific surface area, the electrochemical kinetics of the Te redox reaction are significantly improved. As a result, the Te-MoO2 /NC electrode exhibits superior cycling stability and a high specific capacity of 493 mAh g-1 at 0.1 A g-1 . Meanwhile, the conversion mechanism is systematically explored using a variety of ex situ characterization methods. Therefore, this study provides a novel approach for enhancing the kinetics of the Te redox reaction in aqueous Zn-Te batteries.


Anterior tooth caries: dental management considerations in preschool children.
This paper has introduced a child management protocol which incorporates better facial seal of the relative analgesic nosepiece together with rubber dam control which effectively allows the operator to concentrate on the precise delivery of the restorative option. The benefits of immediate treatment must be weighed up against the potential psychological distress of not having benefited from the luxury of behavioural management intervention.


[Changes of risk factors in patients with coronary heart disease after in-patient rehabilitation].
Rehabilitation therapy of patients with coronary heart disease (CHD) aims at reducing cardiovascular risk factors and at maintaining reduced risk factor levels. The aim of this analysis was to assess to what degree current in-patient rehabilitation and subsequent out-patient care by general practitioners (GPs) achieve these goals. As part of the KAROLA-Study (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung = Long-term success of cardiological rehabilitation therapy) 1206 patients between 30 and 70 years of age (mean age: male: 58.3 years, female: 60.8 years) who underwent in-patient rehabilitation due to CHD between January 1999 and May 2000 were recruited. Risk factor levels were assessed at the beginning and at the end of in-patient rehabilitation, and patients were re-examined one year after discharge using a standardised exam conducted by the GPs. Patients with increased risk factor levels at the time of admission showed significant improvements in the following risk factors during rehabilitation: Body mass index (-0.7 kg/m(2)), diastolic blood pressure (-10 mmHg), systolic blood pressure (-10 mmHg), total cholesterol (-73 mg/dl), LDL-cholesterol (-63 mg/dl), HDL-cholesterol (+ 3 mg/dl), triglycerides (-70 mg/dl). One year after discharge, however, all but one of the parameters (LDL-cholesterol) had re-increased significantly. The prescription of lipid lowering drugs rose from 56 % to 76 % during rehabilitation therapy and remained constant during the first year after discharge. During in-patient rehabilitation therapy important risk factors of CHD improved on average, but these improvements are only partly sustained in the long term. To ensure long-term success of rehabilitation measures more effective maintenance of risk factor modification in subsequent out-patient care is needed.


Environmental transmission of violent criminal behavior in siblings: a Swedish national study.
BACKGROUND. Violent criminal behaviour (VCB) runs strongly in families partly because of shared environmental factors. Can we clarify the environmental processes that contribute to similarity of risk for VCB in siblings? We assessed VCB from the Swedish National Crime Register for the years 1973-2011 in siblings born 1950-1991. We examined by conditional logistic and Cox proportional hazard regression, respectively, whether resemblance for VCB in sibling pairs was influenced by their age difference and whether VCB was more strongly 'transmitted' from older→younger versus younger→older siblings. In our best-fit logistic model, for each year of age difference in full sibling pairs, the risk for VCB in the sibling of a case versus control proband declined by 2.6% [95% confidence interval (CI) 2.2-3.0]. In our best-fit Cox model, the hazard rate for VCB in a sibling when the affected proband was older versus younger was 1.4, 2.1 and 2.9 respectively for a 1-, 5- and 10-year difference in siblings. Controlling for genetic effects by examining only full siblings, sibling resemblance for risk for VCB was significantly greater in pairs closer versus more distant in age. Older siblings more strongly transmitted risk for VCB to their younger siblings than vice versa. These results strongly support the importance of familial-environmental influences on VCB and provide some insight into the possible mechanisms at work.


Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study.
Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history. A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records. After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25). Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.


Efficacy of Endotherapy in the Treatment of Pain Associated With Chronic Pancreatitis: A Systematic Review and Meta-Analysis.
Endotherapy is a treatment modality that can be used to manage the pain associated with chronic pancreatitis. The aim of this systematic review and meta-analysis is to evaluate the efficacy of endotherapy in the management of pain associated with chronic pancreatitis. A search of Medline, Pubmed, and Embase databases between 1988 to December 2014 was conducted to evaluate the use of endotherapy for pain relief in patients with chronic pancreatitis. We included large prospective studies, randomized controlled trials and retrospective analyses. Exclusion criteria included studies not written in the English language, small studies with less than 10 patients, case series/case reports and studies that enrolled patients treated with dual therapies including surgery or celiac plexus neurolysis. In addition, a subgroup analysis was conducted to evaluate studies that included patients with pancreatic duct strictures. A meta-analysis was performed and the data on pain relief was subsequently extracted, pooled, and analyzed. I2 index estimates were calculated to test for variability and heterogeneity across the included studies. Our final analysis included sixteen studies, comprising 1498 patients. Eleven studies presented data on immediate pain relief after endotherapy and twelve studies presented data on both immediate and long term pain relief (mean follow up was 47.4 months). The compiled result of the sixteen studies for immediate pain relief demonstrated 88% efficacy (95% NT CI [81.0%, 94%]) of endotherapy. Similarly, analysis of pain relief on long term follow-up showed a 67% efficacy of endotherapy (95% NT CI [58%, 76%]). The compiled complication rate for endotherapy in this review was 7.85% per ERCP/endotherapeutic procedure and the most common complications were acute pancreatitis, stent occlusion and stent migration. Endotherapy is beneficial for both immediate and long term management of pain associated with chronic pancreatitis. The efficacy of endotherapy decreases over time as assessed by evaluating pain relief on long term follow up. Given the considerable heterogeneity of reported data, additional prospective and standardized multicenter studies need to be conducted to evaluate the efficacy of this modality in controlling pain associated with chronic pancreatitis.


A Bayesian Genomic Multi-output Regressor Stacking Model for Predicting Multi-trait Multi-environment Plant Breeding Data.
In this paper we propose a Bayesian multi-output regressor stacking (BMORS) model that is a generalization of the multi-trait regressor stacking method. The proposed BMORS model consists of two stages: in the first stage, a univariate genomic best linear unbiased prediction (GBLUP including genotype × environment interaction GE) model is implemented for each of the L traits under study; then the predictions of all traits are included as covariates in the second stage, by implementing a Ridge regression model. The main objectives of this research were to study alternative models to the existing multi-trait multi-environment (BMTME) model with respect to (1) genomic-enabled prediction accuracy, and (2) potential advantages in terms of computing resources and implementation. We compared the predictions of the BMORS model to those of the univariate GBLUP model using 7 maize and wheat datasets. We found that the proposed BMORS produced similar predictions to the univariate GBLUP model and to the BMTME model in terms of prediction accuracy; however, the best predictions were obtained under the BMTME model. In terms of computing resources, we found that the BMORS is at least 9 times faster than the BMTME method. Based on our empirical findings, the proposed BMORS model is an alternative for predicting multi-trait and multi-environment data, which are very common in genomic-enabled prediction in plant and animal breeding programs.


Effects of breeder age and egg weight on morphological changes in the small intestine of chicks during the hatch window.
1. The objective of the study was to investigate the effects of breeder age and egg weight on hatching performance and morphological changes in segments of the small intestine of broiler chicks during a 21 h hatch window. 2. Eggs from Ross broiler breeder flocks aged 29 (young) and 48 weeks (old) were classified as light (LE) or heavy (HE) and incubated at the same conditions. At 475 h of incubation, eggs were checked every 3 h to determine time of external pipping and hatching. The first 42 chicks to emerge from each group were weighed and chick length was measured and 14 chicks from each group were sampled to collect residual yolk and intestine segments. The rest of chicks were placed back in the incubator and chick weight and length were measured individually at 9, 15 and 21 h after chicks hatched. At the end of 21 h, 14 chicks from each group were sampled again and the same procedure was followed. 3. The HE chicks pipped and hatched later than LE, regardless of breeder age. From hatch to the end of the hatch window, chick weight, but not yolk-free chick weight, gradually reduced. Relative residual yolk weight of chicks from both egg weights was similar at hatch, however, yolk sac utilisation was higher for LE chicks during the 21 h post-hatch period. At hatch, jejunum and ileum villus development was very similar for HE and LE chicks but greater development was observed for villus area with an increase in the jejunum villus length, width and goblet cell numbers in HE chicks. 4. The longest jejunum villus and the widest duodenum and jejunum villus were obtained for HE chicks from old breeders indicating that HE chicks from old breeders would have a greater surface area for nutrient absorption.


Prophylactic activity of a phenanthrene methanol (WR 33063) and a quinoline methanol (WR 30090) in human malaria.
WR 33063 (3-bromo-10-[alpha-hydroxy-beta-(n, n-diheptylamino)ethyl]-phenanthrene hydrochloride) and WR 30090 (6,8-dichloro-2,3,4-dichlorphenyl-di-n-butylaminoethyl-4- quinolinemethanol hydrochloride) were tested for suppressive prophylactic effect on induced malaria in nonimmune volunteers living in an area where malaria is not naturally transmitted. Doses of 800 mg of WR 33063 and 690 or 460 mg of WR 30090 were given at weekly intervals to men exposed on the day of the first dose to mosquitoes heavily infected with chloroquine- and pyrimethamine-resistant strains of Plasmodium falciparum. WR 33063 did not interfere with early development of infection, but WR 30090 given for 8 weeks provided suppressive cures in 20 of 26 men. P. vivax infections similarly induced broke through WR 30090 treatment in 4 of 15 men, and most of the remainder experienced malaria after completion of the prophylactic course. No side effects of treatment were observed.


Is there something other than imatinib mesilate in therapeutic options for GIST?
In the last decade, the introduction of imatinib mesilate into the clinical practice has resulted in a dramatic improvement in the treatment of gastrointestinal stromal tumor (GIST). Nowadays, the median overall survival in patients with advanced disease has increased to 5 years, while recent Phase III trials demonstrated that imatinib mesilate can be successfully employed as adjuvant therapy in patients at significant risk of recurrence. Despite these good results, the emergence of secondary resistance represents the main cause of treatment failure. In recent years, many efforts have been made in search of drugs to overcome imatinib mesilate resistance; some of these have been employed as second-line treatment or salvage therapy. Summarized and investigated in this paper are the results obtained by imatinib mesilate in advanced and adjuvant setting, the role of sunitinib malate as second-line therapy in imatinib mesilate-resistant patients and the clinical results concerning new drugs, mainly tyrosine-kinase inhibitors. Current research on novel therapeutic agents, as third-line treatments in GIST, is ongoing. However, despite the promising results obtained with the new molecules, imatinib mesilate remains the cornerstone in the medical treatment of GIST and to date no other drugs can replace it.


A short history of the microsurgery training and research laboratory at Gulhane Military Medical Academy.
Microsurgical techniques have played a crucial role in the development of neurosurgery and microsurgical education has an involuting role to gain surgical competence in neurosurgery. Microsurgery laboratory at Gulhane Military Medical Academy (GMMA) was established in 1985 by Prof. Erdener Timurkaynak within the Research-Development Building. From the beginning, education of the surgeons in microsurgery has been regarded as the essential function of this center, but many experimental and anatomical researches have also taken place in this laboratory. Over the past twenty-five years, 288 courses had been held in the microsurgical laboratory and more than 1000 surgeons from different fields and specialties were trained. Many of them conducted hundreds of research projects and published scientific papers during this period. This laboratory enters in the 21st century as a dynamic research and education center committed to the continuing delivery of education, as well as ongoing research of microsurgery for the coming 100 years.